The work proposed in this application deals with regulation of growth of neoplastic and control cells. More specifically we want to investigate the effect of serum proteins or substances carried by serum proteins on the metabolism and proliferation of neoplastic cells. We have published results providing evidence that a serum protein disappears from the serum of tumor-bearing animals as the tumor increases in size and that this factor stimulates, preferentially, metabolism of hepatoma cells as opposed to liver cells. It is the objective of the proposed work to develop these observations further. We would like to show that this protein accumulates preferentially in or on hepatoma cells, and we would like to provide evidence that this serum factor does promote cell proliferation. We further would like to determine whether the factor stimulates neoplastic cells preferentially. It is hoped that these investigations will give us some insight into the mode of action of the serum protein. To meet these objectives we plan to purify relatively large quantities of the serum factor from normal rat serum. We will attempt to label the factor in vivo or in vitro and we will prepare an antibody against it. Some of the purified factor will be used to study its growth promoting activity with cells in culture. Labeled factor will be used to determine accumulation in specific tissues in the animal and the site of interaction on cells. Antibody will be used to study the site of synthesis. A long range aim of this work is to find a way of inhibiting the synthesis of this protein or to prevent it from exerting its effect. BIBLIOGRAPHIC REFERENCES: Effect of a Normal Serum Protein Absent from Hepatoma-Bearing Animals on Cell Cultures. Dolan, M. L., Coetzee, M. L., Spangler, M., and Ove, P. J. of the Natl. Cancer Instit. 54, 163-169, 1975. DNA Synthesis in Membrane-Denuded Nuclei and Nuclear Fractions from Host Liver and Morris Hepatomas. Coetzee, M. L., Spangler, M., Morris, H. P., and Ove, P. Cancer Research 35, 2752-2761, 1975.